Use of EDG Receptor Binding Agents in Cancer

Abstract

Provided is a method for treating solid tumors, e.g tumor invasiveness, and particularly inhibiting or controlling deregulated angiogenesis, using a sphingosine-1-phosphate receptor agonist, optionally in combination with a chemotherapeutic agent. The invention also comprises a combination of a sphingosine-1-phosphate receptor agonist with a chemotherapeutic agent.

1 . A method for inhibiting or controlling deregulated angiogenesis, e.g. sphingosine-1-phosphate (S1P) mediated angiogenesis, in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a S1P receptor agonist. 
     
     
         2 . A method for preventing or treating diseases mediated by a neo-angiogenesis process or associated with deregulated angiogenesis in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a S1P receptor agonist. 
     
     
         3 . A method according to  claim 1  comprising co-administration, concomitantly or in sequence, of a therapeutically effective amount of a S1P receptor agonist and a second drug substance, said second drug substance being a chemotherapeutic agent. 
     
     
         4 . A method according to  claim 2  comprising co-administration, concomitantly or in sequence, of a therapeutically effective amount of a S1P receptor agonist and a second drug substance, said second drug substance being a chemotherapeutic agent. 
     
     
         5 . The method according to  claim 1 , wherein the S1P receptor agonist is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form. 
     
     
         6 . The method according to  claim 2 , wherein the S1P receptor agonist is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form. 
     
     
         7 . A pharmaceutical combination comprising a) a first agent which is a S1P receptor agonist and b) a co-agent. 
     
     
         8 . A combination according to  claim 7 , wherein the co-agent is selected from
 i. an aromatase inhibitor,   ii. an antiestrogen, an anti-androgen or a gonadorelin agonist,   iii. a topoisomerase I inhibitor or a topoisomerase II inhibitor,   iv. a microtubule active agent, an alkylating agent, an antineoplastic antimetabolite or a platin compound,   v. a compound targeting/decreasing a protein or lipid kinase activity or a protein or lipid phosphatase activity, a further anti-angiogenic compound or a compound which induces cell differentiation processes,   vi. a bradykinin 1 receptor or an angiotensin II antagonist,   vii. a cyclooxygenase inhibitor, a bisphosphonate, a histone deacetylase inhibitor, a heparanase inhibitor, a biological response modifier, an ubiquitination inhibitor, or an inhibitor which blocks anti-apoptotic pathways,   viii. an inhibitor of Ras oncogenic isoforms,   ix. a telomerase inhibitor,   x. a protease inhibitor, a matrix metalloproteinase inhibitor, a methionine aminopeptidase inhibitor, or a proteosome inhibitor, and/or   xi) a mTOR inhibitor.   
     
     
         9 . The method according to  claim 7 , wherein the S1P receptor agonist is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form. 
     
     
         10 . The method according to  claim 8 , wherein the S1P receptor agonist is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form.